PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation.
The identification of novel factors regulating human T helper (Th)-cell differentiation into functionally distinct Th1 and Th2 subsets is important for understanding the mechanisms behind human autoimmune and allergic diseases. We have identified a protein of relevant evolutionary and lymphoid interest (PRELI), a novel protein that induces oxidative stress and a mitochondrial apoptosis pathway in human primary Th cells. We also demonstrated that PRELI inhibits Th2-cell development and down-regulates signal transducer and activator of transcription 6 (STAT6), a key transcription factor driving Th2 differentiation. Our data suggest that calpain, an oxidative stress-induced cysteine protease, is involved in the PRELI-induced down-regulation of STAT6. Moreover, we observed that a strong T-cell receptor (TCR) stimulus induces expression of PRELI and inhibits Th2 development. Our results suggest that PRELI is involved in a mechanism wherein the strength of the TCR stimulus influences the polarization of Th cells. This study identifies PRELI as a novel factor influencing the human primary Th-cell death and differentiation.
Tahvanainen
Johanna
J
Turku Centre for Biotechnology, University of Turku and Abo Akademi, Turku, Finland.
Kallonen
Teemu
T
Lähteenmäki
Hanna
H
Heiskanen
Kaisa M
KM
Westermarck
Jukka
J
Rao
Kanury V S
KV
Lahesmaa
Riitta
R
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D024101:Mitochondrial Proteins; C102194:PRELID1 protein, human; D011506:Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D002154:Calpain